AUTOMATED MOLECULAR MECHANICS PARAMETERIZATION WITH SIMULTANEOUS UTILIZATION OF EXPERIMENTAL AND QUANTUM-MECHANICAL DATA

A general set of procedures for automated parameterization of molecula r mechanics force fields is presented. The current implementation for MacroModel force fields can easily be adapted to other programs runnin g under Unix. Several variants of numerical Newton-Raphson and simplex methodologies are used to fit simultaneously both experimental and qu antum mechanical data. In a sample parameterization of ethane, 24 diff erent modes of combining various sources of reference data are compare d. The best cost/performance ratio for generating quantum mechanical s ource data was obtained with the B3LYP/6-31G method. The best optimiz ation strategy consists of initial subset optimizations with a modifie d simplex method, followed by Newton-Raphson optimization using Lagran ge multipliers. (C) 1998 John Wiley & Sons, Inc.